Viral Cytopathic Effects
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Direct answer
Viruses leave fingerprints in the nucleus, the cytoplasm and the relationships between cells, and most diagnoses on H&E rest on recognising whose fingerprint it is. Herpes simplex and varicella-zoster produce the three Ms — multinucleation, nuclear moulding and chromatin margination with Cowdry type A inclusions; cytomegalovirus produces owl-eye intranuclear inclusions with cytoplasmic counterparts in endothelium and glands; HPV produces koilocytes; adenovirus produces smudge cells; BK polyomavirus produces decoy cells in urine. Measles syncs cells into Warthin-Finkeldey giants and parvovirus B19 arrests erythropoiesis in giant pronormoblasts. Immunohistochemistry and in-situ hybridisation (EBER) confirm what morphology suggests.
What you must remember
- Herpes group (HSV/VZV): multinucleation, moulding, margination — the three Ms; ground-glass nuclei and Cowdry A (eosinophilic intranuclear inclusion with a clear halo); acantholytic vesicles; Tzanck smear shows the same.
- CMV: large basophilic intranuclear "owl-eye" inclusion with a perinuclear halo plus basophilic cytoplasmic inclusions; tropism for endothelium, epithelium (gut ulcers, lung) and retina; IHC confirms; treated with ganciclovir/valganciclovir.
- HPV: koilocytosis — binucleation, wrinkled raisin-like nuclei, perinuclear halos; p16 block positivity marks transforming infections in dysplasia; E6/E7 degrade p53 and RB.
- Adenovirus: basophilic nuclear inclusions that obliterate the nucleus — "smudge cells"; haemorrhagic cystitis, tubulointerstitial nephritis and enteritis in the immunosuppressed.
- BK polyomavirus (urine): decoy cells — homogeneous ground-glass basophilic intranuclear inclusions that mould the nucleus, with comet cells (inclusion plus urothelial tail); the classic mimic of high-grade urothelial carcinoma in transplant surveillance.
- Measles and parvovirus B19: Warthin-Finkeldey syncytial giant cells (also a follicular dendritic cell phenomenon in lymphoid tissue); parvovirus B19 giant pronormoblasts with intranuclear inclusions — "lantern cells" — in erythroid precursors, causing aplastic crisis.
- Cytoplasmic inclusions: molluscum contagiosum (Henderson-Paterson bodies) and rabies (Negri bodies in Purkinje cells and hippocampal neurons); EBV needs EBER in-situ hybridisation — nasopharyngeal carcinoma, Burkitt lymphoma, PTLD, hairy leukoplakia.
Decoy cells versus carcinoma in a transplant urine
A renal transplant recipient's routine urine cytology returns single cells with large, dark, homogeneous nuclei and high nuclear-to-cytoplasmic ratios — the reflex reading is high-grade urothelial carcinoma, and the reflex is wrong more often than it is right here. Decoy cells show moulded, ground-glass intranuclear inclusions, chromatin margination and sometimes the comet tail of cytoplasm; they lack the coarse irregular chromatin and pleomorphism of carcinoma, and they appear in the setting of BK viraemia with rising viral load and allograft nephropathy risk rather than haematuria with a bladder lesion. The clinical loop closes with imaging and cystoscopy — normal — and a plasma BK PCR that explains everything. The same discipline applies in gut biopsies: CMV inclusions hunt along ulcer bases in endothelium, so an unexplained ulcer in an immunosuppressed patient deserves CMV immunohistochemistry even when H&E looks quiet, because missing it delays ganciclovir that heals the ulcer.
Where students slip
Cowdry type A is assigned to herpes alone in most answers; CMV's intranuclear inclusion is also a Cowdry-type inclusion, and the owl-eye description exists because of its size and halo, not because it leaves the Cowdry family. The second slip is calling every multinucleated giant cell "herpes" — Warthin-Finkeldey cells are measles, and in lymphoid follicles they can appear without clinical measles. Third, koilocytes must be distinguished from glycogenated vacuolation; true koilocytosis carries nuclear atypia — the raisin nucleus — not just a halo. In vivas, the expected add-ons are the confirmatory tools: CMV immunohistochemistry, HPV RNA probes and EBER in-situ hybridisation, each named with its virus, not merely "special stains".
Frequently asked questions
What are the three Ms of herpes infection?
Multinucleation, nuclear moulding and chromatin margination — with Cowdry type A inclusions and ground-glass nuclei.
How are CMV inclusions recognised histologically?
Large basophilic intranuclear owl-eye inclusions with a perinuclear halo, plus cytoplasmic inclusions, in endothelial and epithelial cells; IHC confirms.
What is a decoy cell in urine cytology?
A BK polyomavirus-infected urothelial cell with a homogeneous ground-glass intranuclear inclusion, mimicking high-grade carcinoma in transplant surveillance.
Which virus causes Warthin-Finkeldey giant cells?
Measles — syncytial giant cells with dozens of nuclei, seen in respiratory epithelium and lymphoid tissue.
How is EBV demonstrated in tissue?
EBER in-situ hybridisation, positive in nasopharyngeal carcinoma, Burkitt lymphoma, PTLD and oral hairy leukoplakia.